Biomeditsinskaia Khimiia[JOURNAL]
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200 papers
[Ginsenosides affect the system of Toll-like receptors in the brain of rats under conditions of long-term alcohol withdrawal].
Airapetov MI, Eresko SO, Kochkin DV … +4 more , Nosov AM, Bychkov ER, Lebedev AA, Shabanov PD
Biomed Khim · 2022 Dec · PMID 36573411 · Publisher ↗
Long-term alcohol consumption causes the development of neuroinflammation in various brain structures. One of the mechanisms involved in this process is the increased activity of TLR-signaling intracellular pathways. Stu...
Long-term alcohol consumption causes the development of neuroinflammation in various brain structures. One of the mechanisms involved in this process is the increased activity of TLR-signaling intracellular pathways. Studies confirm the ability of ginseng extract or its individual ginsenosides to reduce the increased activity of TLR-signaling pathways. The aim of our study was to study the effect of the amount of ginsenosides obtained from the extract of the Panax japonicus cell line on the state of the TLR-signaling system in the nucleus accumbens and hippocampus of the rat brain in a model of long-term alcohol consumption during alcohol withdrawal. The results of the study showed that ginsenosides were able to make changes in the TLR signaling system, which has been altered by long-term alcohol consumption. A significant effect of ginsenosides on the level of TLR3 and TLR4 mRNA in the nucleus accumbens was found, while in the hippocampus, ginsenosides significantly affected the level of TLR7 mRNA. The effect of ginsenosides on the level of mRNA of transcription factors and cytokines involved in TLR-signaling was evaluated. Thus, results of our study confirm that ginsenosides are able to influence the state of TLR-signaling pathways, but this effect is multidirectional in relation to different brain structures. In the future, it seems interesting to evaluate the role of individual ginsenosides in relation to genes of TLR-signaling, as well as the effect of ginsenosides on other brain structures.
[Study of the efficiency of cellular accumulation of doxorubicin supplied with a targeted delivery system based on phospholipid nanoparticles with integrin-directed peptide].
Kostryukova LV, Tereshkina YA, Tikhonova EG … +3 more , Sanzhakov MA, Bobrova DV, Khudoklinova YY
Biomed Khim · 2022 Dec · PMID 36573410 · Publisher ↗
Chemotherapeutic agents containing targeted systems are a promising pathway to increase the effectiveness of glioblastoma treatment. Specific proteins characterized by increased expression on the surface of tumor cells a...
Chemotherapeutic agents containing targeted systems are a promising pathway to increase the effectiveness of glioblastoma treatment. Specific proteins characterized by increased expression on the surface of tumor cells are considered as possible targets. Integrin αvβ3 is one of such proteins on the cell surface. It effectively binds the cyclic Arg-Gly-Asp (cRGD) peptide. In this study, the cRGD peptide-modified doxorubicin (Dox) phospholipid composition was investigated. The particle size of this composition was 43.76±2.09 nm, the ζ-potential was 4.33±0.54 mV. Dox was almost completely incorporated into the nanoparticles (99.7±0.58%). The drug release increased in an acidic medium (at pH 5.0 of about 35±3.2%). The total accumulation and internalization of Dox used the composition of phospholipid nanoparticles with the targeted vector was 1.4-fold higher as compared to the free form. In the HeLa cell line (not expressing αvβ3 integrin) this effect was not observed. These results suggest the prospects of using the cyclic RGD peptide in the delivery of Dox to glioblastoma cells and the feasibility of further investigation of the mechanism of action of the entire composition as a whole.
[Characterization and biological activity of new 4-oxo-1,4-dihydrocinnoline-based inhibitors of the tyrosine phosphatase PTP1B and TCPTP].
Derkach KV, Zakharova IO, Bakhtyukov AA … +3 more , Sorokoumov VN, Kuznetsova VS, Shpakov AO
Biomed Khim · 2022 Dec · PMID 36573409 · Publisher ↗
Functional disorders in obesity are largely due to a decrease in tissue sensitivity to insulin and leptin. One of the ways to restore it is inhibition of protein phosphotyrosine phosphatase 1B (PTP1B) and T-cell protein...
Functional disorders in obesity are largely due to a decrease in tissue sensitivity to insulin and leptin. One of the ways to restore it is inhibition of protein phosphotyrosine phosphatase 1B (PTP1B) and T-cell protein phosphotyrosine phosphatase (TCPTP), negative regulators of the insulin and leptin signaling. Despite progress in the development of inhibitors of these phosphatases, commercial preparations based on them have not been developed yet, and the mechanisms of action are poorly understood. The aim of the work was to study the effect of new derivatives of 4-oxo-1,4-dihydrocinnoline (PI04, PI06, PI07) on the activity of PTP1B and TCPTP, as well as to study the effect of their five-day administration (i.p., 10 mg/kg/day) to Wistar rats with diet-induced obesity on body weight and fat, metabolic and hormonal parameters, and gene expression of phosphatase and insulin and leptin receptors in the liver. It has been shown that PI04 is a mild, low selective inhibitor of both phosphatases (PTP1B, IC50=3.42(2.60-4.51) μM; TCPTP, IC50=4.16(3.49-4.95) μM), while PI06 and PI07 preferentially inhibit PTP1B (IC50=3.55 (2.63-4.78) μM) and TCPTP (IC50=1.45(1.18-1.78) μM), respectively. PI04 significantly reduced food intake, body weight and fat, attenuated hyperglycemia, normalized glucose tolerance, basal and glucose-stimulated levels of insulin and leptin, and insulin resistance index. Despite the anorexigenic effect, PI06 and PI07 were less effective, having little effect on glucose homeostasis and insulin sensitivity. PI04 significantly increased the expression of the PTP1B and TCPTP genes and decreased the expression of the insulin and leptin receptor genes. PI06 and PI07 had little effect on these indicators. Thus, PI04, the inhibitor of PTP1B and TCPTP phosphatases, restored metabolic and hormonal parameters in obese rats with greater efficiency than inhibitors of PTP1B (PI06) and TCPTP (PI07). This indicates the prospect of creating mixed PTP1B/TCPTP inhibitors for correction of metabolic disorders.
[Extracellular vesicles for diagnosis and therapy of gliomas: problems and opportunities].
Filin AA, Chernysheva AA, Pavlova GV … +2 more , Loshhenov VB, Gurina OI
Biomed Khim · 2022 Dec · PMID 36573408 · Publisher ↗
Glioblastoma is a primary brain tumor and one of the most aggressive malignant neoplasms. The prognosis remains poor with a short survival period after diagnosis even in the case of timely detection and early treatment w...
Glioblastoma is a primary brain tumor and one of the most aggressive malignant neoplasms. The prognosis remains poor with a short survival period after diagnosis even in the case of timely detection and early treatment with the use of advanced chemotherapy, radiation therapy and surgical treatment. In this regard, the research of the main pathogenetic links in the glioblastoma development continues. The current focus is on studying the molecular characteristics of tumours, including the analysis of extracellular vesicles, which play an essential role in intercellular communication processes. In this review, in order to provide up-to-date information on the role of extracellular vesicles in the diagnosis and therapy of gliomas, the analysis of the achieved results of Russian and foreign research related to this area has been carried out. The main goal of this review is to describe the features of extracellular vesicles as the containers and glioma marker transporters, as well as nucleic acids used in diagnosis and therapy.
[Molecular basis of biological activity of polysaccharides in COVID-19 associated conditions].
Generalov EA, Simonenko EY, Kulchenko NG … +1 more , Yakovenko LV
Biomed Khim · 2022 Dec · PMID 36573407 · Publisher ↗
The review considers the main molecular biological features of the COVID-19 causative agent, the SARS-CoV-2 virus: life cycle, viral cell penetration strategies, interactions of viral proteins with human proteins, cytopa...
The review considers the main molecular biological features of the COVID-19 causative agent, the SARS-CoV-2 virus: life cycle, viral cell penetration strategies, interactions of viral proteins with human proteins, cytopathic effects. We also analyze pathological conditions that occur both during the course of the COVID-19 disease and after virus elimination. A brief review of the biological activities of polysaccharides isolated from various sources is given, and possible molecular biological mechanisms of these activities are considered. Data analysis shows that polysaccharides are a class of biological molecules with wide potential for use in the treatment of both acute conditions in COVID-19 and post-COVID syndrome.
[Acetylation, methylation, and ubiquitination of proteins in experimental ischemic stroke in mice: a bioinformatics analysis].
Skvortsov VS, Ivanova YO, Voronina AI
Biomed Khim · 2022 Nov · PMID 36373886 · Publisher ↗
The experimental results available in the ProteomeXchange database (accession code PXD016538) (Simats et al. (2020) Molecular and Cellular Proteomics, 19(12), 1921-1936) obtained using a comprehensive multi-omics approac...
The experimental results available in the ProteomeXchange database (accession code PXD016538) (Simats et al. (2020) Molecular and Cellular Proteomics, 19(12), 1921-1936) obtained using a comprehensive multi-omics approach were analyzed in mouse blood to identify potential biomarkers of ischemic stroke. Acetylation, methylation, and ubiquitination were considered as post-translational modifications. The analysis of the significance of changes in the level of protein modification was evaluated for ischemic tissue in comparison with tissue undamaged by stroke and control taken from mice after sham operation. At the level of statistically significant differences according to the Mann-Whitney test (p < 0.05), 2 proteins were found (Q02248 and Q8BL66); for additional 7 proteins, the differences were at the level of a statistical trend (p < 0.1). For 7 of 9 selected proteins there are reports in the literature, for their association with cerebral ischemia.
[A relationship between zinc and anthropometric and metabolic indicators of obesity in the population of young russian men].
Osadchuk LV, Danilenko AD, Osadchuk AV
Biomed Khim · 2022 Nov · PMID 36373885 · Publisher ↗
Trace elements are important factors in human health. Zinc, an essential trace element, is necessary for normal functioning of many body systems where it plays an important role in metabolism. Obesity is accompanied by v...
Trace elements are important factors in human health. Zinc, an essential trace element, is necessary for normal functioning of many body systems where it plays an important role in metabolism. Obesity is accompanied by various metabolic pathologies provoking the development of dyslipidaemia, metabolic syndrome, type 2 diabetes mellitus, arterial hypertension, cardiovascular diseases and cancer. Many studies demonstrate changes in zinc homeostasis in obese men, but the data are conflicting, and a relationship between serum zinc and anthropometric and metabolic indicators remains controversial. In this study we have investigate the relationship between serum zinc level and body mass index (BMI), waist circumference (WC), and some metabolic parameters in Russian men. In 260 young men from the general population (n=268, median age 22 years), serum zinc, triglycerides (TG), total cholesterol (TC), high and low density lipoprotein cholesterol (HDL and LDL), glucose and uric acid levels were determined, as well as body weight, height, waist circumference (WC), and BMI were evaluated. According to BMI, men were divided into four groups: deficient and normal body weight, overweight, obesity. According to WC men were subdivided into two groups: normal and abdominal-visceral type of obesity. The median serum zinc concentration in men of the entire studied population was 20.3 μmol/l, and in men with obesity (BMI≥30) the median serum zinc concentration was higher than in the corresponding value in men with normal weight (30.9 and 20.8 μmol/l, respectively, p<0.01). Serum levels of TG, TC and LDL in obese men were also significantly higher (p<0.01) as compared to men with normal weight. In men with abdominal-visceral obesity, the median serum zinc concentration was significantly higher in comparison with control (26.3 and 19.9 μmol/l, respectively, p<0.01). It is suggested that elevated serum zinc level in obese young men can counter chronic inflammation and oxidative stress caused by increased body fat.
[Lipidomic markers of breast cancer malignant tumor histological types].
Tokareva AO, Chagovets VV, Starodubtseva NL … +4 more , Rodionov VV, Kometova VV, Chingin KS, Frankevich VE
Biomed Khim · 2022 Nov · PMID 36373884 · Publisher ↗
The molecular profile of a tumor is associated with its histological type and can be used both to study the mechanisms of tumor progression and to diagnose it. In this work, changes in the lipid profile of a malignant br...
The molecular profile of a tumor is associated with its histological type and can be used both to study the mechanisms of tumor progression and to diagnose it. In this work, changes in the lipid profile of a malignant breast tumor and the adjacent tissue were studied. The potential possibility of determining the histological type of the tumor by its lipid profile was evaluated. Lipid profiling was performed by reverse-phase chromato-mass-spectrometric analysis the tissue of lipid extract with identification of lipids by characteristic fragments. Potential lipid markers of the histological type of tumor were determined using the Kruskal-Wallis test. Impact of lipid markers was calculated by MetaboAnalyst. Classification models were built by support vector machines with linear kernel and 1-vs-1 architecture. Models were validated by leave-one out cross-validation. Accuracy of models based on microenvironment tissue, were 99% and 75%, accuracy of models, based on tumor tissue, were 90% and 40% for the positive ion mode and negative ion mode respectively. The lipid profile of marginal (adjacent) tissue can be used for identification histological types of breast cancer. Glycerophospholipid metabolism pathway changes were statistically significant in the adjacent tissue and tumor tissue.
[Behavioral and neuroreceptor effects of the racetam derivative GIZh-290 in mouse experimental attention deficit model].
Kovalev GI, Sukhorukova NA, Vasileva EV … +4 more , Kondrakhin EA, Salimov RM, Narkevich VB, Kudrin VS
Biomed Khim · 2022 Nov · PMID 36373883 · Publisher ↗
Behavioral and neurochemical effects of the new racetam derivative GIZh-290 were studied in a mouse attention deficit model (the ED-Low animals subpopulation selected during preliminary behavioral typing in the "closed e...
Behavioral and neurochemical effects of the new racetam derivative GIZh-290 were studied in a mouse attention deficit model (the ED-Low animals subpopulation selected during preliminary behavioral typing in the "closed enriched cross maze" test). Subchronic administration of GIZh-290 (1 mg/kg, 3 mg/kg and 5 mg/kg, intraperitoneally, for 6 days), increased the initially low level of attention in ED-Low animals; the highest selectivity was observed at a dose of 3 mg/kg. Radioligand analysis showed that at this dose, the drug changed density (Bmax) of D2 and GABAB receptors as markers in the pre-frontal cortex of the ED-Low subpopulation to Bmax values observed in the ED-High subpopulation. In the prefrontal cortex of the ED-Low rodents treated with GIZh-290 in dose of 3 mg/kg, there was a normalization of tissue concentrations of both dopamine itself (DA) and its intra- and extracellular metabolites (DOPA/DA and HVA/DA). The obtained results indicate the effectiveness of the studied drug for pharmacotherapy of attention deficit in experimental modeling and impact on potential molecular targets identified in the study.
[Genotoxic stress leads to the proinflammatory response of endothelial cells: an in vitro study].
Sinitsky MY, Sinitskaya AV, Shishkova DK … +1 more , Ponasenko AV
Biomed Khim · 2022 Nov · PMID 36373882 · Publisher ↗
It was shown, that genotoxic stress can trigger endothelial disfunction and atherosclerosis, but the molecular genetic mechanisms of this process are poorly investigated. At the same time, inflammation also plays the imp...
It was shown, that genotoxic stress can trigger endothelial disfunction and atherosclerosis, but the molecular genetic mechanisms of this process are poorly investigated. At the same time, inflammation also plays the important role in atherogenesis. This study aimed access of inflammatory marker expression in the endothelial cells exposed to alkylating mutagen mitomycin C (MMC). Primary human coronary (HCAEC) and internal thoracic artery endothelial cells (HITAEC) exposed to 500 ng/ml MMC (experimental group) and 0.9% NaCl (control) were used in this research. A gene expression profile was evaluated by quantitative reverse transcription PCR after 6 h exposure of endothelial cells to MMC (or 0.9% NaCl) followed by subsequent 24 h incubation in the mutagen-free cell growth media. The cytokine profile of endotheliocytes was studied by dot blotting. We found that MIF, IL-8, MCP-1, IP-10 and PDGFB were upregulated both in HCAEC and HITAEC, while MIP-1β release remained unchanged. TIMP-2 was upregulated in HCAEC but not in HITAEC. sTNF RI was expressed only in HCAEC. According to gene expression analysis, HCAEC exposed to MMC are characterized by the increased mRNA level of IL-8, MCP-1 and IP-10; decreased expression of TIMP-2 and no differences in the expression of MIF, MIP-1β and PDGFB compared to the control. In HITAEC, increased mRNA level of IL-8 and IP-10; decreased expression of MIF and TIMP-2, no differences in the expression of MCP-1, MIP-1β and PDGFB was shown. TNF-RI expression was not detected in both cell lines. Thus, genotoxic stress in endothelial cells induced by MMC leads to differential inflammatory response that can trigger endothelial dysfunction.
[Interactomics of CXXC proteins involved in epigenetic regulation of gene expression].
Ershov PV, Yablokov EO, Mezentsev YV … +1 more , Ivanov AS
Biomed Khim · 2022 Nov · PMID 36373881 · Publisher ↗
Regulation of gene expression is an extremely complex and multicomponent biological phenomenon. Proteins containing the CXXC-domain "zinc fingers" (CXXC-proteins) are master regulators of expression of many genes and hav...
Regulation of gene expression is an extremely complex and multicomponent biological phenomenon. Proteins containing the CXXC-domain "zinc fingers" (CXXC-proteins) are master regulators of expression of many genes and have conserved functions of methylation of DNA bases and histone proteins. CXXC proteins function as a part of multiprotein complexes, which indicates the fundamental importance of studying post-translational regulation through modulation of the protein-protein interaction spectrum (PPI) in both normal and pathological conditions. In this paper we discuss general aspects of the involvement of CXXC proteins and their protein partners in neoplastic processes, both from the literature data and our own studies. Special attention is paid to recent data on the particular interactomics of the CFP1 protein encoded by the CXXC1 gene located on the human chromosome 18. CFP1 is devoid of enzymatic activity and implements epigenetic regulation of expression through binding to chromatin and a certain spectrum of PPIs.
[Changes of a₂-macroglobulin activity and endothelin-1 concentration in tears of rabbits after transplantation of retinal pigment epithelium cells derived from the induced pluripotent stem cells].
Neroeva NV, Neroev VV, Chesnokova NB … +9 more , Katargina LA, Pavlenko TA, Beznos OV, Ilyukhin PA, Utkina OA, Lagarkova MA, Laktionov PP, Bogomazova AN, Kharitonov AE
Biomed Khim · 2022 Nov · PMID 36373880 · Publisher ↗
Retinal diseases accompanied with the dysfunction or death of the retinal pigment epithelial (RPE) cells are widespread, hard to treat, and appear to be a leading case of visual loss and blindness among the persons older...
Retinal diseases accompanied with the dysfunction or death of the retinal pigment epithelial (RPE) cells are widespread, hard to treat, and appear to be a leading case of visual loss and blindness among the persons older than 55 years. Transplantation of RPE cells derived from the induced pluripotent stem cells (IPSC-RPE) is a promising method of therapy for these diseases. To ensure the transplant survival instant follow-up is required. It can be based on biochemical analyses of tear fluid that can be easily non-invasively collected. For the post-transplantation process monitoring we have choosen such polyfunctional bioregulators as α2-macroglobulin (α2-MG) and endothelin-1 (ET-1). RPE atrophy in New Zealand Albino rabbits was modeled via the subretinal injection of bevacizumab. IPSC-RPE in suspension or as a monolayer on the scaffold were transplanted subretinally 1 month after the injection. α2-MG activity and ET-1 concentration in tears were estimated during the first month and after 2, 3 and 7 months after transplantation. On the 7-14 days after transplantation α2-MG activity increased in tears of the both operated and controlateral eye probably as a reaction on the corticosteroid therapy. In 50% rabbits there was one more increase after 2-3 months that could be due to the immune inflammation. Concentration of ET-1 in tears decreased dramatically on the 7-14 days and 7 months after transplantation, and it could have an influence upon the retinal vassal tone. The data obtained show that estimation of bioregulators in tears can help monitoring local metabolic processes after RPE transplantation that is necessary for the opportune, reasonable and focused medicamental correction of post-transplantation process.
[Metabolome profiling in the study of aging processes].
Balashova EE, Trifonova OP, Maslov DL … +3 more , Lichtenberg SR, Lokhov PG, Archakov AI
Biomed Khim · 2022 Nov · PMID 36373879 · Publisher ↗
Aging of a living organism is closely related to systemic metabolic changes. But due to the multilevel and network nature of metabolic pathways, it is difficult to understand these connections. Today, this problem is sol...
Aging of a living organism is closely related to systemic metabolic changes. But due to the multilevel and network nature of metabolic pathways, it is difficult to understand these connections. Today, this problem is solved using one of the main approaches of metabolomics - untargeted metabolome profiling. The purpose of this publication is to systematize the results of metabolomic studies based on such profiling, both in animal models and in humans.
[Zonulin - regulation of tight contacts in the brain and intestine - facts and hypotheses].
Naryzhny SN, Legina OK
Biomed Khim · 2022 Nov · PMID 36373878 · Publisher ↗
In recent years, the interrelationship between the brain and the gut has become an area of high scientific interest. The intestine is responsible not only for digestion, as it contains millions of neurons, its own immune...
In recent years, the interrelationship between the brain and the gut has become an area of high scientific interest. The intestine is responsible not only for digestion, as it contains millions of neurons, its own immune system, and affects the emotional and cognitive processes. The relationship between the gut and the brain suggests that the processes carried out by the gut microbiota play a significant role in the regulation of brain function, and vice versa. A special role here is played by intercellular tight junctions (TJ), where the zonulin protein holds an important place. Zonulin, an unprocessed precursor of mature haptoglobin, is the only physiological modulator of intercellular TJ that can reversibly regulate the permeability of the intestinal (IB) and blood-brain (BBB) barriers in the human body. BBB disruption and altered microbiota composition are associated with many diseases, including neurological disorders and neuroinflammation. That is, there is a gut-brain axis (GBA) - a communication system through which the brain modulates the functions of the gastrointestinal tract (GIT) and vice versa. GBA is based on neuronal, endocrine, and immunological mechanisms that are interconnected at the organismal, organ, cellular, and molecular levels.
[Mechanism of regulation of the constitutive androstane receptor under conditions of modeling oxidative stress in vitro].
Abalenikhina YV, Shchulkin AV, Seidkuliyeva AA … +2 more , Pravkin SK, Yakusheva EN
Biomed Khim · 2022 Aug · PMID 36005848 · Publisher ↗
The constitutive androstane receptor (CAR) is a nuclear receptor that participates in the regulation of biotransformation of toxic substances and metabolic processes. The mechanisms of expression changes of CAR under con...
The constitutive androstane receptor (CAR) is a nuclear receptor that participates in the regulation of biotransformation of toxic substances and metabolic processes. The mechanisms of expression changes of CAR under conditions of oxidative stress (OS) have not been studied yet and this was the purpose of the study. OS was modeled by incubating Caco2 cells with hydrogen peroxide 10-100 μM for 72 h. The amount of CAR was determined by the Western blot, nuclear factor erythroid 2-related factor 2 (Nrf2) was evaluated by a heterogeneous enzyme immunoassay malondialdehyde (MDA), the lipid peroxidation products (LPP) was assayed by a photometric method. Incubation of cells with 10 μM and 50 μM H2O2 led to an increase in the amount of CAR and Nrf2, while incubation with 100 μM H2O2 caused their decrease. Nrf2 inhibition did not influence the CAR content under OS conditions. 10 μM MDA increased the CAR content, 100 μM MDA had no effect, while 150 μM reduced the amount of CAR.
[Coagulation activity of circulating membrane microparticles in patients with cardiovascular diseases].
Antonova OA, Golubeva NV, Yakushkin VV … +5 more , Zyuryaev IT, Krivosheeva EN, Komarov AL, Martynyuk TV, Mazurov AV
Biomed Khim · 2022 Aug · PMID 36005847 · Publisher ↗
Membrane microparticles (MP) are released by activated or damaged cells and are able to accelerate blood clotting (coagulation). MP possess coagulation activity since all of them contain on their surface phosphatidylseri...
Membrane microparticles (MP) are released by activated or damaged cells and are able to accelerate blood clotting (coagulation). MP possess coagulation activity since all of them contain on their surface phosphatidylserine (PS), a substrate for the assembly of coagulation complexes, and some of them tissue factor (TF), the primary initiator of coagulation cascade reactions. We compared the coagulation activity and amount of MP in the blood of healthy donors (n=34) and patients with myocardial infarction (MI) (n=32), advanced atherosclerosis (AA) (n=32) and idiopathic pulmonary arterial hypertension (IPAH) (n=19). Total MP fraction was obtained from blood plasma by sedimentation at 20000 g, 30 min. The coagulation activity of PM isolated from 100 μl of donor and patient plasma was determined using a modified recalcification test. MP were added to substrate plasma devoid of endogenous MF, plasma was recalcified, and clotting was recorded by changes in optical density (A450), determining lag phase (min) and maximum rate (Vmax, %A450/min). MP were counted by flow cytometry as PS+ particles (lactadgerin-FITC staining) smaller than 1 μm and their concentration was expressed as 105 MP/μl plasma. MP in all patient groups accelerated plasma clotting more effectively than donor MP. Lag phase compared with donors (11.8 [11.0-13.1] median and interquartile range) was shorter in patients with AA (8.8 [7.0-10.3], p.
[The effect of rifampicin on the system of Toll-like receptors in the nucleus accumbens of the brain of long-term alcoholized rats during alcohol withdrawal].
Airapetov MI, Eresko SO, Skabelkin DA … +4 more , Iskalieva AR, Lebedev AA, Bychkov ER, Shabanov PD
Biomed Khim · 2022 Aug · PMID 36005846 · Publisher ↗
Nucleus accumbens (NAc) is the ventral part of the striatum of the brain; it is an important part of the mesolimbic pathway involved in the reward system that mediates the formation of various forms of addiction, in part...
Nucleus accumbens (NAc) is the ventral part of the striatum of the brain; it is an important part of the mesolimbic pathway involved in the reward system that mediates the formation of various forms of addiction, in particular alcohol addiction. Neuroimaging data and in vitro studies indicate the development of a pronounced neurodegenerative process in the NAc, with long-term alcohol use, but the key mechanisms mediating this process remain unknown. In recent years, the attention of researchers has been focused on studying the system of Toll-like receptors (TLRs), the increased activity of which is clearly shown in the cerebral cortex and hippocampus during prolonged alcohol exposure, but there is a need to study the role of this system in other brain structures. In this study, we have shown that prolonged alcohol exposure (2 months) with moderate doses of ethanol (2 g/kg) promotes a pronounced increase in the expression of the Tlr4 gene and its endogenous ligand Hmgb1 in NAc during the period of alcohol withdrawal in rats. Injections of rifampicin (100 mg/kg) reduced the elevated expression level of Hmgb1, Tlr4, as well as pro-inflammatory cytokine genes (IL1β, IL6), while the administration of the drug increased the reduced level of mRNA of anti-inflammatory cytokines (IL10, IL11).
[Molecular and biochemical studies of succinate dehydrogenase in rat liver under conditions of alloxan diabetes].
Eprintsev AT, Fedorin DN, Bakarev MY
Biomed Khim · 2022 Aug · PMID 36005845 · Publisher ↗
Experimental alloxan diabetes in rats causes an increase in the activity of liver succinate dehydrogenase (SDH) without changes in its isozyme composition. The observed increase in the catalytic activity of SDH clearly c...
Experimental alloxan diabetes in rats causes an increase in the activity of liver succinate dehydrogenase (SDH) without changes in its isozyme composition. The observed increase in the catalytic activity of SDH clearly correlates with the intensification of transcription of the genes encoding catalytic dimer of SDH. Analysis of the methyl status of the promoters of the genes, encoding the catalytic dimer of SDH in rats under normal and experimental conditions did not reveal any dependence on the level of their expression. The obtained results of bisulfite sequencing indicate a passive role of the epigenetic mechanism of regulation of SDH gene expression in the development of alloxan diabetes. The transcription factor CREB, responsible for of gluconeogenesis in diabetes, may play an important role in the control of the transcriptional activity of the sdha and sdhb genes.
[Influence of intranasally administered insulin on metabolic and hormonal parameters in adult male rats, impaired due to three-day fasting in the early postnatal period].
Derkach KV, Bondareva VM, Shpakov AO
Biomed Khim · 2022 Aug · PMID 36005844 · Publisher ↗
Temporary cessation or restriction of breastfeeding can lead to metabolic disorders in adulthood. However, data on the effect of fasting in the early postnatal period on the functions of the endocrine system in adulthood...
Temporary cessation or restriction of breastfeeding can lead to metabolic disorders in adulthood. However, data on the effect of fasting in the early postnatal period on the functions of the endocrine system in adulthood are rare and contradictory. Approaches for the correction of metabolic and hormonal disorders caused by premature cessation of breastfeeding have not been developed yet. The aim of the work was to study the metabolic and hormonal parameters and changes in the hormonal status of the gonadal and thyroid systems in 10-month-old male rats with interruption of breastfeeding on days P19-P21, as well as to evaluate the restorative effect on them of four weeks of treatment with intranasal insulin (II) administered in the postnatal period (P28-P55) or in adulthood (P183-P210). Lactation interruption has been induced by treatment of lactating females with bromocriptine (10 mg/day/rat, P19-P21). Male rats with temporary cessation of breastfeeding developed characteristic signs of the metabolic syndrome (obesity, dyslipidemia, impaired glucose tolerance, hyperleptinemia), decreased levels of testosterone and thyroid hormones (fT4, tT3) and weakened the synthesis of testosterone and thyroxine, stimulated respectively by GnRH and thyroliberin. This was due to a decrease in the sensitivity of the testes to luteinizing hormone (LH) and the thyroid gland to thyroid-stimulating hormone (TSH). Treatment with II in early ontogenesis reduced body weight and fat, improved lipid profile, sensitivity to insulin, leptin, LH and TSH, restored the levels of testosterone and thyroid hormones and their stimulation by releasing factors. Treatment with II in adulthood normalized the levels of testosterone, thyroid hormones, their stimulation by releasing factors, but had a little effect on metabolic and hormonal parameters. The obtained data point to a wide range of metabolic and hormonal disorders in adult male rats with the "neonatal" model of metabolic syndrome and to the effectiveness of various strategies for their correction using long-term II treatment.
[The key role of the regulatory 19S subunit in changes in the brain proteasome subproteome induced by the neuroprotector isatin].
Buneeva OA, Kopylov AT, Medvedev AE
Biomed Khim · 2022 Aug · PMID 36005843 · Publisher ↗
Isatin (indole-2,3-dione) is an endogenous regulator exhibiting various effects mediated by numerous isatin-binding proteins localized in different compartments of cells of the brain and peripheral tissues. It attenuates...
Isatin (indole-2,3-dione) is an endogenous regulator exhibiting various effects mediated by numerous isatin-binding proteins localized in different compartments of cells of the brain and peripheral tissues. It attenuates manifestations of experimental parkinsonism induced by administration of the MPTP neurotoxin and reduces the movement disorders characteristic of this disease. The molecular mechanisms of the neuroprotective action of isatin include its direct interaction with proteasomes, intracellular supramolecular complexes responsible for the targeted elimination of proteins. Incubation of fractions of 26S and 20S rabbit brain proteasomes, containing the whole spectrum of proteasomal subunits, as well as a number of proteasome-associated proteins, with isatin (100 μM) had a significant impact on the profile of released proteins. In the case of 26S proteasomes containing, in addition to the core part (20S proteasome), 19S regulatory subparticles, incubation with isatin resulted in a more than threefold increase in the number of dissociated proteins. In the case of 20S proteasomes (containing only the 20S core particle), incubation with isatin resulted in a significant decrease in the number of dissociated proteins compared to the control. Our results indicate an important role of the regulatory 19S subunit components in the formation of the proteasome subproteome and the sensitivity of these supramolecular complexes to isatin.
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